With 5.5 percent of participants reporting use, omeprazole is the most commonly prescribed drug with potential depression side effects. Sold under brand names including Prilosec and Losec, omeprazole is a proton pump inhibitor used to treat gastroesophageal reflux disease (GERD) and peptic ulcers. A study published this year concluded that proton-pump inhibitors “might represent a frequent cause of depression in older populations.”

Sold under the brand name Lopressor, metoprolol is a beta-blocker type medication used to treat high blood pressure and heart failure. A 2016 study also found that people using beta-blockers or calcium channel antagonists (another class of blood pressure medication) had significantly higher risk of depression. It was used by 4.9 percent of participants in the study.

An ingredient in a variety of hormonal birth control pills, ethinyl estradiol is also used to treat menopausal symptoms in older women. A concluded that use of hormonal contraception, particularly among adolescents “was associated with subsequent use of antidepressants and a first diagnosis of depression.” It was used by 4.6 percent of participants in the study.

Sold under the brand name Zoloft, sertraline is a selective serotonin reuptake inhibitor (SSRI) class antidepressant. It’s used to treat depression, certain forms of anxiety, and panic disorder. SSRI antidepressants such as Sertraline carry a “black box” warning, the highest level of warning from the U.S. Food and Drug Administration (FDA), because of their potential to induce suicidal thoughts and behaviors in children, adolescents, and young adults up to the age of 25. It was used by 2.8 percent of participants in the study.

Sold under the brand name Neurontin, gabapentin has found use for a broad spectrum of conditions both on- and off-label including seizures, epilepsy, and neuropathic pain. In 2008, the FDA issued a warning on gabapentin and other antiepileptic drugs for potential elevated risk of suicidality. Since the warning was issued, some studies have challenged the FDA’s conclusion and . It was used by 2.4 percent of participants in the study.

Sold as Celexa or Cipramil, citalopram is another antidepressant of the SSRI class. It’s used for the treatment of depression and sometimes prescribed off-label for the treatment of anxiety or panic disorder. SSRI antidepressants such as Citalopram carry a “black box” warning, the highest level of warning from the FDA, because of their potential to induce suicidal thoughts and behaviors in children, adolescents, and young adults up to the age of 25. It was used by 2.4 percent of participants in the study.

Commonly sold as Wellbutrin or Zyban, bupropion is a norepinephrine-dopamine reuptake inhibitor (NDRI) class antidepressant. It’s primarily used for the treatment of depression, but is also used to help people stop smoking. Bupropion also carries a “black box” warning, the highest level of warning from the FDA, because of its potential to induce suicidal thoughts and behaviors in children, adolescents, and young adults up to the age of 25. It was used by 2.2 percent of participants in the study.

Revealing research

To conduct the study, researchers used survey data from 26,192 adults who participated in the National Health and Nutrition Examination Survey. Participants listed medications they were taking and completed a depression screening questionnaire.

Survey data was taken from five 2-year cycles starting in 2005–2006, with the last cycle in 2013–2014. Researchers were then able to examine trends in prescription data between those periods.

“What we found is that adults who are taking these medications were at increased risk of actually having or reporting depression. And the more the medications they were taking, the greater was their risk,” said study author Dr. Mark Olfson, professor of psychiatry and epidemiology at Columbia University.

The reported use of prescription drugs with the potential to cause depression increased from 35 percent to 38.4 percent between 2005 and 2014. Use of drugs with suicidal symptoms also increased during that period from 17.3 percent to 23.5 percent.

Among those taking just one drug with depression side effects, 6.9 percent reported depression. When the number of drugs increased to two, the reported depression also climbed to 9.5 percent. In participants taking three or more, the prevalence of depression was 15.3 percent. Those who didn’t take any drugs had a depression rate of 4.7 percent.

Olfson and his team also identified that the number of people surveyed in 2013–2014 who were taking more drugs had also increased from those surveyed in 2005–2006. The number of participants taking three or more drugs with depression as a potential adverse effect climbed from 6.9 percent during the earlier period to 9.5 percent in the latter. Participants taking three or more drugs with suicide symptoms increased from 1.9 percent to 3.3 percent.

However, Olfson says that while the data shows a clear association between these drugs and the prevalence of depression, the evidence doesn’t prove a causal link.

Pedro Dago, a psychiatrist and specialist in mood disorders at Northwestern University’s Feinberg School of Medicine who wasn’t involved in the study, underscored this point.

“Those are associations, and you have to keep that in mind. It’s very, very difficult in psychiatry and in medicine in general to establish cause and effect. It’s hard to do. That study speaks to an association but, as the authors acknowledge, they cannot establish cause and effect at all,” said Dago.

He added, “It’s clinically meaningful, but not that meaningful.”

Olfson also warns that the results of his research don’t mean people should abruptly stop taking their medication.

While not necessarily having direct clinical implications, the study adds an important new facet to the country’s fevered discussion around suicide and mental health. With the United States still reeling from a rash of high-profile suicides, including those of designer Kate Spade and TV personality Anthony Bourdain, there is a demand for answers.

The Centers for Disease Control and Prevention also issued a well-publicized report indicating that suicide rates increased in the United States by more than 30 percent in the last two decades.

However, the report didn’t explain why this was happening.

“Turns out it’s a very difficult thing to study epidemiologically and you’re left with a set of correlations, and to really establish causal factors for population-wide trends is exceedingly difficult,” said Olfson.

For better or worse, Olfson’s new research will likely complicate that assessment further.

Still, the fact remains that many Americans are likely taking one or more drugs with depression or suicide symptoms as a potential side effect without knowing it.

“It’s my hope that by building greater awareness that there are a large number of commonly prescribed medications that have depression as an adverse effect — and many people are actually taking several of them — that in that kind of a clinical context, primary care docs will consider that these medications may be one factor that is contributing to their patient’s depression,” said Olfson.